Systems and method for deep brain stimulation therapy

ABSTRACT

A system and method for performing deep brain stimulation (DBS) therapy are provided. The method and system include pre-operatively acquiring at least one pre-operative image of the brain with at least one imaging sub-system and determining a location of a Nucleus Basalls of Meynert (NBM) for therapy in the at least one pre-operative image, and intra-operatively acquiring at least one intra-operative image of the brain after obtaining an access opening through the skull. The method and system further provide performing surgical planning based on the pre-operative image in the intra-operative image, advancing a lead having DBS electrodes on the lead to a target position proximate to or within the NBM area, and coupling the lead to an implantable pulse generator (IPG) configured to deliver DBS pulses through the DBS electrodes to the NBM. Further, the IPG is configured to deliver DBS pulses for treating symptoms associated with Alzheimer&#39;s disease.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a division of U.S. patent application Ser. No. 14/244,596, filedApr. 3, 2014.

FIELD OF THE INVENTION

Embodiments of the present disclosure generally relate to deep brainstimulation (DBS) therapy, and more particularly to treatment ofsymptoms associated with Alzheimer's disease (AD).

BACKGROUND OF THE INVENTION

DBS represents a therapy that has been shown to treat and relievecertain neurological disorders, such as Parkinson's disease, tremors,dystonia, psychiatric illness, and the like. In general, DBS may includeelectrically stimulating certain areas of the brain to alter orotherwise affect behavior to alleviate the effects of a neurologicaldisorder. The behavioral effects of brain stimulation typically dependon a location of a stimulating electrode within the brain. For example,DBS of the Nucleus Accumbens (NAcc) has shown to reduce depression,anhedonia, and anxiety.

DBS is being used for treating cognitive disorders such as Alzheimer'sDisease (AD). AD is one of the most common degenerative dementias, andis accompanied by cognitive deficits in neuropsychiatric symptoms suchas depression, apathy, agitation, and the like that involve degenerationof neural circuits. There are currently two targets for DBS therapy intreating AD, specifically for improving memory, the fornix and theentorhinal cortex. The fornix as a target for DBS in the treatment of ADis described in, for example, U.S. Patent Application Publication No.2013/0231709, entitled, “COGNITIVE FUNCTION WITHIN THE HUMAN BRAIN.” DBSof the fornix has been shown to enhance neurogenesis and the release ofneurotrophic factors in the hippocampus. DBS of the entorhinal cortexand the hippocampus for AD treatment are described, for example, in WO2012/083254, entitled, “SITE SPECIFIC DEEP BRAIN STIMULATION FORENHANCEMENT OF MEMORY.”

Nucleus Basalis of Meynert (NBM) is a group of neurons located at thebase of the forebrain, anterior to the hypothalamus, and ventral to thebasal ganglia adjacent to the NAcc. The NBM provides cholinergicinnervation to the cerebral cortex by distributing the neurotransmitteracetylcholine (ACh) via cholinergic fibers projecting to the hippocampusand amygdala. Reduced ACh levels has been shown to impair cognitivefunction affecting learning and memory in a similar way as with patientsdiagnosed with AD.

Accordingly, a system and method is needed for DBS of the NBM to serveas a treatment for AD.

SUMMARY

In accordance with one embodiment, a method for performing deep brainstimulation (DBS) therapy is provided. The method includespre-operatively acquiring at least one pre-operative image of the brainof a patient with at least one imaging sub-system. The method alsoincludes determining a location of a Nucleus Basalis of Meynert (NBM)for therapy in the at least one pre-operative image, andintra-operatively acquiring at least one intra-operative image of thebrain after obtaining an access opening through the skull of thepatient. The method further provides, performing surgical planning basedon the pre-operative image in the intra-operative image. Additionally,the method includes advancing a lead having DBS electrodes on the leadto a target position proximate to or within the NBM area, and couplingthe lead to an implantable pulse generator (IPG) configured to deliverDBS pulses through the DBS electrodes to the NBM. Further, the IPG isconfigured to deliver DBS pulses for treating symptoms associated withAlzheimer's disease.

In an embodiment, a system for performing deep brain stimulation (DBS)therapy is described with a surgical planning (SP) workstation having anInput configured to receive at least one pre-operative image of thebrain of the patient with at least one imaging sub-system. The SPworkstation is configured to permit the user to determine a location ofa Nucleus Basalis of Meynert (NBM) for therapy in the at least onepre-operative image. The SP workstation also has an input configured toreceive at least one intra-operative image of the brain after obtainingan access opening through its goal of the patient. Additionally, the SPworkstation is configured to perform surgical planning based on thepre-operative image in the intra-operative image. The system alsoincludes a lead having deep brain stimulation (DBS) electrodes on thelead. The DBS electrodes are configured to be advanced to a targetposition proximate to or within the NBM area. Further, the systemincludes an implantable pulse generator (IPG) coupled to the lead. TheIPG is configured to deliver DBS pulses through the DBS electrodes tothe NBM. The IPG is also configured to deliver DBS pulses for treatingsymptoms associated with Alzheimer's disease.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a schematic diagram of a system for performing deepbrain stimulation (DBS) therapy in accordance with an embodiment of thepresent disclosure.

FIG. 2 illustrates a perspective view of a stereotactic frame secured toa head of a patient in accordance with an embodiment of the presentdisclosure.

FIG. 3 illustrates a lateral view of a probe in accordance with anembodiment of the present disclosure.

FIG. 4 illustrates an enlarged view of an implantable DBS system inaccordance with an embodiment of the present disclosure.

FIG. 5 illustrates a flowchart of a method for performing DBS therapy inaccordance with an embodiment of the present disclosure.

FIG. 6 illustrates a simplified diagram of a surgical drill being usedin conjunction with a stereotactic frame to drill a bore hole through askull of a patient, according to an embodiment of the present disclosure

FIG. 7 illustrates a simplified diagram of a patient with a securedstereotactic frame being imaged by an imaging subsystem, according to anembodiment of the present disclosure.

FIG. 8a illustrates a merged image of the pre-operative image andintra-operative image shown on a display, according to an embodiment ofthe present disclosure.

FIG. 8b illustrates a merged image of the pre-operative image andintra-operative image shown on a display, according to an embodiment ofthe present disclosure.

FIG. 9a illustrates the merged image of FIG. 8b from a coronal shown ona display, according to an embodiment of the present disclosure.

FIG. 9b illustrates the merged image of FIG. 8b from a coronal shown ona display, according to an embodiment of the present disclosure.

FIG. 10 graphically illustrates of a DBS pulse, according to anembodiment of the present disclosure.

FIG. 11 illustrates a DBS lead proximate to a Nucleus Basilis of Meynertand a Nucleus Accumbens, according to an embodiment of the presentdisclosure.

FIG. 12 graphically illustrates DBS pulses, according to an embodimentof the present disclosure.

FIG. 13 illustrates a DBS lead proximate to a Nucleus Basilis of Meynertand a Nucleus Accumbens, according to an embodiment of the presentdisclosure.

DETAILED DESCRIPTION

Embodiments described herein provide systems and methods for performingdeep brain stimulation (DBS) therapy and/or manufacturing or using a DBSsystem. Embodiments described herein further provide methods forstimulating a Nucleus Basalis of Meynert (NBM) using a surgical planning(SP) work station to determine a location of the NBM from at least onepre-operative image of a brain of a patient, and for positioning a leadwith DBS electrodes proximate to or within the NBM based on thepre-operative image and an intra-operative image. An implantable pulsegenerator (IPG) is coupled to the lead to deliver DBS pulses through theDBS electrodes for treating symptoms associated with Alzheimer's Disease(AD). In certain embodiments, the lead is positioned such that the DBSelectrodes deliver DBS pulses, within an energy trajectory, to the NBMand to a Nucleus Accumbens (NAcc) for treating psychiatric symptoms. Incertain embodiments, the DBS electrodes on the lead are configured tohave a first and second electrodes sets.

While multiple embodiments are described, still other embodiments of thedescribed subject matter will become apparent to those skilled in theart from the following detailed description and drawings, which show anddescribe illustrative embodiments of disclosed inventive subject matter.As will be realized, the inventive subject matter is capable ofmodifications in various aspects, all without departing from the spiritand scope of the described subject matter. Accordingly, the drawings anddetailed description are to be regarded as illustrative in nature andnot restrictive.

FIG. 1 illustrates a schematic diagram of a system 100 for performingdeep brain stimulation (DBS) therapy, according to an embodiment of thepresent disclosure. The system 100 may include one or more imagingsub-systems 104 configured to acquire one or more pre-operative imagesand one or more intra-operative images of a brain of a patient 120. Theimaging sub-system 104 may include one or more of an x-ray, fluoroscope,CT, MRI, positron emission tomography (PET), ultrasound, or other suchimaging systems. For example, the image sub-system 104 may includeComputed Tomography (CT) imaging and Magnetic Resonance Imaging (MRI)systems. In general, the imaging sub-system 104 may include a radiationsource or generator and a radiation sensor or detector.

The system 100 may also include a surgical planning (SP) workstation102. The SP workstation 102 may include a set of input and/or outputterminals within an I/O interface 132 and may contain a display module106 and a registration module 118.

The I/O interface 132 sends/receives data or signals between the SPworkstation 102 to external sub-systems or interfaces such as theimaging sub-system 104, a user interface 130, a positioning sub-system114, a control unit 116, a programmer unit 136, and a display 112.Additionally or alternatively, the I/O interface 132 may format the datasignals to the respective protocols of the destination.

For example, the I/O interface 132 may include an input configured toreceive at least one pre-operative image from the imaging sub-system104. The imaging sub-system 104 may send the pre-operative image along aserial line. The I/O interface 132 may configure the input todeserialize the line (e.g., transport to a parallel bus) to beinterpreted by the SP workstation 102.

The display module 106 may be configured to display the pre-operativeimage and/or the intra-operative image onto the display 112 through theI/O interface 132. The display 112 may be or include a monitor, screen,television, or the like. The display module 106 allows a user (e.g.,doctor, clinician) to determine the location of the NBM for DBS therapyby viewing the pre-operative image of the brain on the display 112. Forexample, the imaging sub-system 104 may use an MRI imaging modality toobtain the pre-operative image showing a coronel plane of a head of thepatient 120. The pre-operative image is received by the display module106 through the I/O interface 132. The display module 106 configures oradjusts a resolution, an aspect ratio, a contrast, a codec, or the likeof the pre-operative image in order for the pre-operative image to bedisplayed on the display 112. Once the pre-operative image is on thedisplay 112, the user may view or analyze the pre-operative image tolocate the NBM. Optionally, the user may, through the user interface130, adjust the contrast, zoom in/out on a select or predeterminedcoordinate, or the like of the pre-operative image shown on the display112. The user interface 130 may be or include a handheld device having adisplay and input members, such as keys, a touchscreen, and/or the like.Alternatively, the interface 130 may be or include a keyboard, mouse, ortouchscreen of the computer, tablet, or the like. Additionally, oralternatively, the user may, through the user interface 130, overlay agraphical marker (e.g., an ‘x’, cross hairs) to indicate a biologicalstructure for a DBS target such as, for example, the NBM.

The registration module 118 may be configured to register thepre-operative and intra-operative images. Optionally, the registrationmodule 118 may merge the pre-operative and intra-operative imagesforming a single image to be displayed on the display 112 using asoftware algorithm. Additionally, or alternatively, the registrationmodule 118 may register the pre-operative and/or intra-operative imageswith a brain structure atlas (e.g., Talairach atlas) to aid in theidentification of the DBS target.

The SP workstation 102 may be in communication with the control unit116. The control unit 116 may include a driving mechanism controlled bythe user through the user interface 130. The driving mechanism mayoperatively control the movement of a probe 128 relative to the patient120. The probe 128 may be operatively connected to a stereotactic frame122 secured to the head of the patient 120.

FIG. 2 shows a perspective view of one embodiment of the stereotacticframe 122 shown secured to the patient 120 in FIG. 1. The stereotacticframe 122 may include a circular band 242 configured to be positionedaround a portion of the head of the patient 120. A positioning device244 is secured to the circular band 242 through opposed rotatable mounts250. The positioning device 244 may include opposed linear beams 248coupled to the rotatable mounts 250. The position device 244 may alsoinclude a semi-circular beam 246 that is moveably secured to the opposedlinear beams 248, which allows the semi-circular beam 246 tobi-directionally traverse along the opposed linear beams 248.

A platform 252 is slidably secured to the semi-circular beam 246. Theplatform 252 is configured to be moved to different areas by traversingthe platform 252 along the semi-circular beam 244. The platform 252 mayinclude an upper guide member 254 and a lower guide member 256. Theupper and lower guide members 254 and 256 are aligned with respect to aninsertion axis 257. The semi-circular beam 246 and the linear beams 248may include scale markings 258 that are configured to provide anaccurate measure of the position of the upper and lower guide members254 and 256 relative to the platform 252, the angular position of theplatform 252 relative to the semi-circular beam 246, and the rotationalposition of the semi-circular beam 246 relative to the circular band242. As such, the orientation of the insertion axis 257 and anypositions relative to the upper and lower guide members 254 and 256 tothe circular band 246 may be correlated.

The stereotactic frame 122 shown in FIG. 2 is just one example of aframe that may be used with embodiments of the present disclosure.Various other types of frames may be used with respect to embodiments ofthe present disclosure. For example, the stereotactic frame may beconstructed as described in FIG. 2B of application title “SYSTEMS ANDMETHODS FOR PERFORMING DEEP BRAIN STIMULATION” (U.S. patent applicationSer. No. 14/222,301, filed Mar. 21, 2014), which is expresslyincorporated herein by reference in its entirety.

The system 100 may also include an array of position sensors 126 withinthe vicinity of the head of the patient 120. The position sensors 126are operatively coupled to the positioning sub-system 114. For example,the position sensors 126 may be positioned within a housing situated onor underneath a platform 124 on which the patient 120 rests. Theposition sensors 126 may include one or more transmitters configured toradiate a field, such as an electromagnetic field, within the vicinityof the patient 120. The field radiated by the transmitters is detectedby a position detector of the probe 128, which is monitored by thepositioning sub-system 114.

FIG. 3 illustrates a lateral view of the probe 128 according to oneembodiment of the present disclosure. It should be noted that variousother types of probe or catheter structures may be used with respect toembodiments of the present disclosure. For example, the positioningprobes may be constructed as described in FIGS. 5-8 of application title“SYSTEMS AND METHODS FOR PERFORMING DEEP BRAIN STIMULATION” (U.S. patentapplication Ser. No. 14/222,301, filed Mar. 21, 2014), which isexpressly incorporated herein by reference in its entirety. The probe128 may be used to position one or more implantable DBS systems 304within a predetermined implantation distance of one or more DBS targets.The probe 128 includes a guide tube 302 defining an internal passage,which the implantable DBS system 304 may traverse through. The guidetube 302 may be formed from a flexible plastic, silicone rubber,nitinol, or the like.

An enlarged illustration of an embodiment of the implantable DBS system304 is illustrated in FIG. 4. The implantable DBS system 304 includes aDBS lead 410 on the distal end of the implantable DBS system 304 coupledto an implantable pulse generator (IPG) 450 that is adapted to generateelectrical pulses, or DBS pulses. The IPG typically comprises a metallichousing that encloses a controller 451, pulse generating circuitry 452,a charging coil 453, a battery 454, far-field and/or near fieldcommunication circuitry 455, battery charging circuitry 456, switchingcircuitry 457, and the like. The controller 451 may include amicrocontroller or other suitable processor for controlling the variousother components of the DBS lead 304. Software code is typically storedin memory of the IPG 450 for execution by the microcontroller orprocessor to control the various components of the DBS lead 304.

Electrical pulses (e.g., DBS pulses) are generated within the IPG 450through respective pulse generating circuitry 452 and are provided toswitching circuitry 457. The switching circuitry 457 connects to outputsof the IPG 450. Electrical connectors (e.g., “Bal-Seal” connectors)within a DBS lead body 472 and/or within the IPG “header” portion of theIPG 450, as known in the art, may be employed to conduct the DBS pulsestowards the DBS lead 410. The DBS lead body 472 may be electricallycoupled to the IPG header portion of the IPG 450 through one or moreterminals. Thereby, the DBS pulses originating from the IPG 450 areprovided to the DBS lead 410. The DBS pulses are then conducted throughconductors within the DBS lead 410 and applied to tissue (e.g., the DBStarget) of the patient 120 via DBS electrodes 411 a-d.

The DBS electrodes 411 a-d may be positioned along a horizontal axis 402of the DBS lead 410, and are angularly positioned about the horizontalaxis 402 so the DBS electrodes 411 a-d do not overlap. The DBSelectrodes 411 a-d may be in the shape of a ring such that each DBSelectrode 411 a-d continuously covers the circumference of the exteriorsurface of the DBS lead 410. Each of the DBS electrodes 411 a-d areseparated by non-conducting rings 418, which electrically isolate eachelectrode 411 a-d from an adjacent electrode 411 a-d. The non-conductingrings 418 may include one or more insulative materials and/orbiocompatible materials to allow the DBS lead 410 to be implantableproximate to or within the DBS target. Non-limiting examples of suchmaterials include polyimide, polyetheretherketone (PEEK), polyethyleneterephthalate (PET) film (also known as polyester or Mylar),polytetrafluoroethylene (PTFE) (e.g., Teflon), or parylene coating,polyether bloc amides, polyurethane. The DBS electrodes 411 a-d may beconfigured to emit the DBS pulse in an outward radial directionproximate to or within the DBS target. Additionally, or alternatively,the DBS electrodes 411 a-d may be in the shape of a split ornon-continuous ring such that the DBS pulse may be directed in anoutward radial direction adjacent to the DBS electrodes 411 a-d.Examples of a fabrication process of the DBS electrodes 411 a-d isdisclosed in U.S. Patent Application Publication No. 2011/0072657,entitled, “METHOD OF FABRICATING STIMULATION LEAD FOR APPLYINGELECTRICAL STIMULATION TO TISSUE OF A PATIENT,” which is expresslyincorporated herein by reference.

It should be noted the DBS electrodes 411 a-d may be in various otherformations, for example, in a planar formation on a paddle structure asdisclosed in U.S. patent application Ser. No. 14/198,260, filed Mar. 5,2014, entitled, “PADDLE LEADS FOR NEUROSTIMULATION AND METHOD OFDELIVERING THE SAME,” which is expressly incorporated herein byreference.

The DBS lead 410 may comprise a DBS lead body 472 of insulative materialabout a plurality of conductors within the material that extend from aproximal end of lead 410, proximate to the IPG 450, to its distal end.The conductors electrically couple a plurality of the DBS electrodes 411a-d to a plurality of terminals (not shown) of the DBS lead 410. Theterminals are adapted to receive electrical pulses (e.g., DBS pulses)and the DBS electrodes 411 a-d are adapted to apply the DBS pulses tothe DBS target of the patient 120. Also, sensing of physiologicalsignals may occur through the DBS electrodes 411, the conductors, andthe terminals. It should be noted that although the DBS lead 410 isdepicted with four DBS electrodes 411 a-d, the DBS lead 410 may includeany suitable number of DBS electrodes 411 a-d (e.g., less than four,more than four) as well as terminals, and internal conductors.

Additionally, or alternatively, various sensors (e.g., a positiondetector 306, a radiopaque fiducial 308) may be located near the distalend of the DBS lead 410 and electrically coupled to terminals throughconductors within the DBS lead body 472. For example, the positiondetector 306 may be secured to the distal end of the DBS lead 410. Theposition detector 306 may include one or more coils that are configuredto detect the radiation field, such as an electromagnetic field, emittedby the position sensors 126 (FIG. 1). The position detector 306 may bein communication with the positioning sub-system 114, for example,through the communication circuitry 455 via a DBS connector 305. Theposition detector 306 may communicate position measurements of theposition detector 306, which may be related to the radiation fieldstrength detected by the position detector 306.

In another example, the radiopaque fiducial 308 may be secured to thedistal end of the DBS lead 410 and/or the position detector 306. Theradiopaque fiducial 308 may be a ball formed of platinum, titanium, orthe like, which resists or absorbs relatively less electromagneticradiation than tissue surrounding the DBS target. Thereby, when imagedby the imaging sub-system 104 (e.g., the intra-operative image) theradiopaque fiducial 308 will be more apparent and/or distinguishablefrom the surrounding tissue by the user when viewing the display 112.Additionally or alternatively, the radiopaque fiducial 308 may belocated at various other positions of the probe 128 and/or the DBS leadbody 472 along the horizontal axis 402 (e.g., at the IPG 450 header, amidpoint of the implantable DBS system 304).

Although not required for all embodiments, the DBS lead body 472 of theDBS lead 410 may be fabricated to flex and elongate upon implantation oradvancing within the brain of the patient 120 towards the DBS target andmovements of the patient 120 after implantation. By fabricating the DBSlead body 472, according to some embodiments, the DBS lead body 472 or aportion thereof is capable of elastic elongation under relatively lowstretching forces. Also, after removal of the stretching force, the leadbody 472 may be capable of resuming its original length and profile. Forexample, the lead body may stretch 10%, 20%, 25%, 35%, or even up orabove to 50% at forces of about 0.5, 1.0, and/or 2.0 pounds ofstretching force. Fabrication techniques and material characteristicsfor “body compliant” leads are disclosed in greater detail in U.S.Provisional Patent Application No. 60/788,518, entitled “Lead BodyManufacturing,” which is expressly incorporated herein by reference.

For implementation of the components within the IPG 450, a processor andassociated charge control circuitry for an IPG is described in U.S. Pat.No. 7,571,007, entitled “SYSTEMS AND METHODS FOR USE IN PULSEGENERATION,” which is expressly incorporated herein by reference.Circuitry for recharging a rechargeable battery (e.g., battery chargingcircuitry 456) of an IPG using inductive coupling and external chargingcircuits are described in U.S. Pat. No. 7,212,110, entitled “IMPLANTABLEDEVICE AND SYSTEM FOR WIRELESS COMMUNICATION,” which is expresslyincorporated herein by reference.

An example and discussion of “constant current” pulse generatingcircuitry (e.g., pulse generating circuitry 452) is provided in U.S.Patent Application Publication No. 2006/0170486 entitled “PULSEGENERATOR HAVING AN EFFICIENT FRACTIONAL VOLTAGE CONVERTER AND METHOD OFUSE,” which is expressly incorporated herein by reference. One ormultiple sets of such circuitry may be provided within the IPG 450.Different DBS pulses on different electrodes 411 a-d may be generatedusing a single set of pulse generating circuitry 452 using consecutivelygenerated pulses according to a “multi-stimset program” as is known inthe art. Complex pulse parameters may be employed such as thosedescribed in U.S. Pat. No. 7,228,179, entitled “Method and apparatus forproviding complex tissue stimulation patterns,” and International PatentPublication Number WO 2001/093953 A1, entitled “NEUROMODULATION THERAPYSYSTEM.” which are expressly incorporated herein by reference.Alternatively, multiple sets of such circuitry may be employed toprovide DBS pulse patterns that include simultaneously generated anddelivered stimulation pulses through various electrodes of one or moreDBS leads as is also known in the art. Various sets of parameters maydefine the pulse characteristics and pulse timing for the DBS pulsesapplied to the various electrodes 411 a-d as is known in the art.Although constant current pulse generating circuitry is contemplated forsome embodiments, any other suitable type of pulse generating circuitrymay be employed such as constant voltage pulse generating circuitry.

The programmer unit 116 (FIG. 1) may be implemented to charge/rechargethe battery 454 of the IPG 450 (although a separate recharging devicecould alternatively be employed) and to program the IPG 450 on the DBSpulse specifications while implanted within the patient 120. Although,in alternative embodiments separate programmer devices may be employedfor charging and/or programming the implantable DBS system 304. Theprogrammer unit 136 may be a processor-based system that possesseswireless communication capabilities. Software may be stored within anon-transitory memory of the programmer unit 136, which may be executedby the processor to control the various operations of the programmerunit 136. A “wand” 138 may be electrically connected to the programmerunit 116 through suitable electrical connectors (not shown). Theelectrical connectors may be electrically connected to a telemetrycomponent (e.g., inductor coil, RF transceiver) at the distal end ofwand 138 through respective wires (not shown) allowing bi-directionalcommunication with the IPG 450. Optionally, in some embodiments, thewand 138 may comprise one or more temperature sensors for use duringcharging operations.

The user may initiate communication with the IPG 450 by placing the wand138 proximate to the implantable DBS system 304 or the head of thepatient 120 when implanted. Preferably, the placement of the wand 138allows the telemetry system of the wand 138 to be aligned with thefar-field and/or near field communication circuitry 455 of the IPG 450.The programmer unit 136 may be controlled by the user (e.g., doctor,clinician) through the user interface 130 allowing the user to interactwith the IPG 450. The user interface 130 may permit the user to moveelectrical stimulation along and/or across one or more of the DBSlead(s) 410 using different DBS electrode 411 a-d combinations, forexample, as described in U.S. Patent Application Publication No.2009/0326608, entitled “METHOD OF ELECTRICALLY STIMULATING TISSUE OF APATIENT BY SHIFTING A LOCUS OF STIMULATION AND SYSTEM EMPLOYING THESAME,” which is expressly incorporated herein by reference.

Also, the programmer unit 136 may permit operation of the IPG 450according to one or more stimulation programs to treat the patient'sdisorder(s) (e.g., AD). Each stimulation program may include one or moresets of stimulation parameters of the DBS pulse including pulseamplitude, pulse width, pulse frequency or inter-pulse period, pulserepetition parameter (e.g., number of times for a given pulse to berepeated for respective stimset during execution of program), biphasicpulses, monophasic pulses, etc. The IPG 450 modifies its internalparameters in response to the control signals from the programmer unit136 to vary the stimulation characteristics of the stimulation pulsestransmitted through the DBS lead 410 to the tissue of the patient.Neurostimulation systems, stimsets, and multi-stimset programs arediscussed in PCT Publication No. WO 01/93953, entitled “NEUROMODULATIONTHERAPY SYSTEM,” and U.S. Pat. No. 7,228,179, entitled “METHOD ANDAPPARATUS FOR PROVIDING COMPLEX TISSUE STIMULATION PATTERNS,” which areexpressly incorporated herein by reference.

FIG. 5 is a flowchart illustrating a method 500 of performing deep brainstimulation (DBS) therapy. The method 500, for example, may employstructures or aspects of various embodiments (e.g., systems and/ormethods) discussed herein. For example, the lead may be similar to theDBS lead 410 (FIG. 4) or may include other features, such as thosedescribed or referenced herein. In various embodiments, certain steps(or operations) may be omitted or added, certain steps may be combined,certain steps may be performed simultaneously, certain steps may beperformed concurrently, certain steps may be split into multiple steps,certain steps may be performed in a different order, or certain steps orseries of steps may be re-performed in an iterative fashion.Furthermore, it is noted that the following is just one possible methodof performing DBS therapy. It should be noted, other methods may beused.

The method 500 includes acquiring (at 502) at least one pre-operativeimage of a brain of the patient with at least one imaging sub-system,and determining (at 504) a location of a Nucleus Basalis of Meynert(NBM) for therapy within the pre-operative image(s). For example, thepre-operative image of the brain of the patient 120 may be acquired fromthe imaging sub-system 104 (e.g., MRI) before surgically implanting, forexample, the implantable DBS system 304. The imaging sub-system 104 mayreceive an instruction to acquire the pre-operative image from the user(e.g., doctor, nurse) directly or through the SP workstation 102 throughthe I/O interface 132. The SP workstation 102 may receive thepre-operative image from the imaging sub-system 104 through an input ofthe I/O interface 132. The registration module 118 may register thepre-operative image with a predetermined brain structure atlas, such asa Talairach atlas, to aid the user in determining the location of theDBS target, for example, the NBM. Optionally, the user may select thebrain structure atlas and DBS target from the user interface 130. Thedisplay module 118 may receive the registered pre-operative image fromthe registration module 118 and configure the pre-operative image to bedisplayed or viewed on the display 112.

Additionally, or alternatively, the display module 112 may overlay amarker or graphic on the pre-operative image when displayed on thedisplay 112 identifying the DBS target. For example, the pre-operativeimage is registered with a Montreal Neurological Institute (MNI) atlasby the registration module 118 allowing structures to be located usingMNI coordinates. The user may select the DBS target as the NBM or MNIcoordinates representing the location of the NBM. The display module 112may overlay the marker or graphic identifying the location of thecoordinates representing the NBM.

In an embodiment, prior to the pre-operative image, anatomical markersmay be positioned on the head of the patient 120 to assist in accuratelyregistering the image with the brain structure atlas or subsequentimages (e.g., intra-operative image(s)) of the patient 120. Theanatomical markers may be placed on a cortical surface of the patient120.

The method 500 includes acquiring (at 506) at least one intro-operativeimage of the brain after obtaining an access opening 604 through a skull602 of the patient 120. For example, FIG. 6 illustrates a simplifieddiagram of a surgical drill 624 being used in conjunction with thestereotactic frame 122 to obtain the access opening (e.g., bore hole)604 through the skull 602 of the patient 120, according to an embodimentof the present disclosure. The location of the access opening 604 may bedetermined through the pre-operative image. The surgical drill 624 mayinclude a main housing 630 operatively connected to a drill bit 632 thatis guided into position through one or more guide members 634 and 636 ofthe stereotactic frame 122. Additionally, or alternatively, the surgicaldrill 624 may be secured to the platform 252. Once in position, thesurgical drill 624 is operated to form the access opening 604 throughthe skull 602. The size of the access opening 604 may be large enough toallow the probe 128 to be advanced into position (e.g., proximate to theDBS target, within the DBS target). Optionally, the surgical drill 624may be operatively coupled to the control unit 116 allowing the user tooperate the surgical drill 624 through the user interface 130. Theaccess opening 604 may be formed through the skull 602 to expose thecortex of the brain.

Once the access opening 604 is formed, the surgical drill 624 may beremoved from the stereotactic frame 122. FIG. 7 illustrates a simplifieddiagram of the patient 120 with the secured stereotactic frame 122 beingimaged by an imaging sub-system 702 (e.g., CT scanner), according to anembodiment of the present disclosure. For example, the imagingsub-system 702 may be connected to the SP workstation 102 through theI/O interface 132. The head of the patient 120, with the access opening604, is positioned within an imaging area 705 located between an emitter706 and a detector 704. The imaging sub-system 702 may receive aninstruction to acquire the intra-operative image from the user (e.g.,doctor, nurse) directly or through the SP workstation 102 through theI/O interface 132. The SP workstation 102 may receive theintra-operative image from the imaging sub-system 702 through an inputof the I/O interface 132. Additionally, or alternatively, the imagingsub-system 702 may acquire additional intra-operative images of the headof the patient 120. Optionally, the imaging sub-system 702 may be thesame imaging sub-system 104 shown in FIG. 1 and described above.

The method 500 includes performing (at 508) surgical planning based onthe pre-operative image(s) and the intra-operative image(s). Forexample, once the SP workstation 102 receives the intra-operative image,from the image sub-system 702, the registration module 118 may registerand/or merge the pre-operative image with the intra-operative image todetermine implant coordinates for the DBS lead 410. Optionally, theregistration module 118 may register the merged image of thepre-operative image with a brain atlas. FIG. 8a illustrates a mergedimage 800 of the pre-operative image and intra-operative image asdisplayed on the display 112, according to an embodiment of the presentdisclosure. The merged image 800 may include a graphic or mark 802indicating the location of the DBS target, such as the NBM. The mergedimage 800 may also indicate the location of the access point 604 and thelocation of the probe 128 external to the head of the patient 120.Additionally, the merged image 800 may display numeral coordinates ofthe DBS target and the access point 604 as Cartesian coordinates basedon the axes 806 (e.g., latero-lateral axis (x), dorso-ventral axis (y),rostro-caudal axis (z)) and/or based on the brain structure atlas thatmay be registered with the merged image 800. Alternatively, thecoordinates may be based on a polar coordinate system.

Optionally, the merged image 800 may indicate the predeterminedimplantation distance from the DBS target or implant coordinates 808 ofthe DBS lead 410. The predetermined implantation distance or implantcoordinates 808 may be based on the effective range of the DBS pulsesemitted from the DBS electrodes 411 a-d to stimulate the DBS target. Theeffective range of the DBS pulse may be based on the amplitude of theDBS pulse and the distance between the surface area of the DBS targetand the DBS electrodes 411 a-d. It should be noted that as the DBSpulses traverses through the surrounding tissue of the DBS lead 410 awayfrom the DBS electrodes 411 a-d, the amplitude of the DBS pulsedecreases due to the resistance of the surrounding tissue. The change inthe DBS pulse amplitude may reduce the effectiveness of the DBS pulse instimulating the DBS target. For example, the DBS pulses emitted from theDBS electrodes 411 a-d may be configured to have a pulse amplitude of 10milli-amperes (mA). Preferably, the DBS target may be within 5.0 mm ofthe DBS electrodes 411 a-d to effectively stimulate the DBS target bythe DBS pulse. It should be noted, that increasing the DBS pulseamplitude may increase the effective distance available as an optionbetween the DBS electrodes 411 a-d and the DBS target to effectivelystimulate the DBS target. Conversely, when the DBS pulse amplitude isdecreased the effective distance to stimulate the DBS target alsodecreases. For example, the DBS pulse having a pulse amplitude of 1 mAwould preferably be closer to the DBS target relative to a DBS pulsehaving a pulse amplitude of 10 mA.

The method 500 includes advancing (at 510) the DBS lead 410 with thedeep brain stimulation (DBS) electrodes 411 a-d to the target position(e.g., implant coordinates 808) proximate to or within the NBM area 802.For example, the probe 128 may be guided into the skull 602 of thepatient 120 by the stereotactic frame 122 (shown in FIG. 7). A drivingmechanism 708, controlled by the control unit 116, may advance the probe128 into the skull 602 of the patient. As shown in FIG. 8a , the distalend of the probe 128, proximate to the brain 804, may include aradiopaque fiducial 810. The radiopaque fiducial 810 may be used toregister and/or track a position of the probe 128 as the probe 128advances within the brain 804. Once the distal end or the radiopaquefiducial 810 reaches the implant coordinates 808, the DBS lead 410 andthe DBS lead body 472 may be advanced through the guide tube 302 by thedriving mechanism. The radiopaque fiducial 308, similar to theradiopaque fiducial 810, may be used to track a position of the DBS lead410 as the radiopaque fiducial 308 advances through the guide tube 302destine for the implantation coordinates 808. Once the distal end or theradiopaque fiducial 308 reaches the implantation coordinates 808, asshown in FIG. 8b , the guide tube 302 may be removed leaving the DBSlead 410 with the DBS electrodes 411 a-d and the DBS lead body 472 inposition. Optionally, the radiopaque fiducial 308 at the distal end ofthe DBS lead 410 or the DBS lead 410 alone may be tracked in subsequentintra-operative image(s) to monitor any post implantation displacementor to confirm the DBS lead 410 is implanted within the implantationcoordinates.

It should be noted, that even though a single DBS lead 410 is describedbeing implanted into the patient 120 in other embodiments, a pluralityof DBS leads 410 and 938 may be advanced into a plurality of differentimplantation coordinates 808 and 912. FIG. 9a illustrates a coronalplane merged image 900 (parallel to the latero-lateral axis (x)) fromthe merged image 800 of patient 120 shown in FIG. 8b . However, themerged image 900 may also include an additional implantation coordinate912 proximate to or within an alternative DBS target location. Thealternative DBS target location may be a second NBM area 908. FIG. 9billustrates a second DBS lead 938 advanced into position through theguide tube 302, using the method described above, as the guide tube 302is being removed through a second access point 902. Optionally, the sameaccess point (e.g., access point 604) may be used to advance the firstand second DBS leads 410 and 938 to the implantation coordinates 808 and912, respectively.

The method 500 includes coupling (at 512) the DBS lead 410 to theimplantable pulse generator (IPG) 450. For example, as described above,the IPG 450 may be electrically coupled to the DBS lead 410 throughconductors from the IPG header through the DBS lead body 472 to the DBSlead 410.

The method 500 includes configuring (at 514) the IPG 450 to deliver DBSpulses for treating symptoms associated with AD and configuring (at 516)the IPG to deliver DBS pulses through the DBS electrodes to the NBM. Forexample, as described above, the IPG 450 may be programmed by theprogrammer unit 136 to emit DBS pulses from the DBS electrodes 411 a-din accordance with a stimulation program for treating AD symptoms (e.g.,impairment of cognitive functions) by stimulating the NBM.

FIG. 10 illustrates a graphical representation of a DBS pulse 1002emitted from at least one of the DBS electrodes 411 a-d with a surfacearea proximate to the NDM to stimulate or increase acetylcholine (Ach)levels, which improves cognitive functions (a symptom of AD).Optionally, in alternative embodiments the surface area of the DBSelectrodes 411 a-d may be within the NDM. The vertical axis 1006represents current or the flow of electric charge from the DBS electrode411 a-d to the surrounding tissue (e.g., the NDM). The horizontal axis1004 represents time. The DBS pulse 1002 is shown as a biphasic pulsewith a positive current amplitude 1010 and a negative current amplitude1012 within a set pulse width 1008. The differing current amplitudes maybe dependent on a state, specifically a cathode or anode state of theDBS electrode 411 a-d.

For example, the DBS pulse 1002 is emitted from the DBS electrode 411 aof the DBS lead 410. The DBS electrode 411 a may receive the DBS pulse1002 from the IPG 450 through the electrical conductors of the IPGheader and the DBS lead body 472 in accordance with the stimulationprogram. The stimulation program may determine that the DBS pulse 1002may have a pulse width 1008 of 150 microseconds (μsec) and an amplitude1010 of 10 mA. The pulse width 1008 of the DBS pulse 1002 is separatedinto two transition phases an anode phase 1014 and a cathode phase 1016.Each of the phases 1014 and 1016 may be approximately 75 μsec in length.To create the biphasic pulse the IPG 450, through the switchingcircuitry 457, may transition the DBS electrode 411 a between the anodeand cathode state. During the anode state the DBS electrode 411 a may beelectrically coupled via the switching circuitry 457 to an energystorage device, such as a capacitor or battery. Thereby, the DBSelectrode 411 a may emit electric charge radially outward toward the NBMat the positive current amplitude 1010 during the anode phase 1014.

Conversely, during the cathode state the DBS electrode 411 a may beelectrically coupled via the switching circuitry 457 to ground or aground plane. Thereby, the DBS electrode 411 a may receive electriccharge from surrounding tissue or adjacent DBS electrodes 411 b-d thatare emitting electric charge shown as the negative current amplitude1012 during the cathode phase 1016. It should be noted that a transition1018 between the anode and cathode phases 1014 and 1016 is shown in FIG.10 as a vertical line (e.g., instantaneous switching), however, in otherembodiments the transition 1018 may be a period of time greater thanzero.

It should again be noted that the above electrical specifications (e.g.,type of pulse, amplitude, frequency, and other electricalcharacteristics) are for illustrative purposes only. In alternativeembodiments the electrical specifications may be greater than or lowerthan described above/below. For example, the pulse width 1008 may begreater (e.g., 200 μsec) than or lesser (e.g., 50 μsec, 75 μsec) thandescribed above.

Optionally, a DBS lead may be positioned to deliver DBS pulses tomultiple DBS targets, such as both of the NBM and the Nucleus Accumbens(NAcc). As described above, the NAcc is positioned adjacent to the NBMand may be stimulated to treat psychiatric symptoms such as depression,anhedonia, and anxiety, which may be additional symptoms of patientssuffering from AD. FIG. 11 illustrates the DBS lead 410 positioned atimplantation coordinates such that the surface area of the DBS lead 410is proximate to both of the DBS targets, such as the NBM 1104 and theNAcc 1102. Optionally, the implantation coordinates may be within theDBS targets such that the DBS lead 410 may be positioned within the NBM1104 and the NAcc 1102. The position of the DBS lead 410 allows two setsor combinations of DBS electrodes, the DBS electrodes 411 c-d and theDBS electrodes 411 a-b, to have energy trajectories 1110 and 1111overlap the NAcc 1102 and NBM 1102, respectively. The energytrajectories 1110 and 1111 may represent an area or distance from theDBS electrodes 411 c-d and 411 a-b, respectively, to the NAcc 1102 andNBM 1102 that a DBS pulse emitted from the DBS electrodes 411 c-d and411 a-b may be propagated through the surrounding tissue and stimulatethe NAcc 1102 and the NBM 1102. The area or distance from energytrajectories 1110 and 1111 may be increased or decreased by adjustingthe amplitude of the DBS pulse, as described above.

FIG. 12 illustrates a graphical representation of DBS pulses 1210, 1212,1214, and 1216 emitted from the DBS electrodes 411 a-d, respectively.The DBS pulses 1210 and 1212 represent the set of DBS electrodes 411 a-bthat stimulate the NBM 1104. The DBS pulses 1214 and 1216 represent theset of DBS electrodes 411 c-d that stimulate the NAcc 1102. The verticalaxis 1203 represents a current amplitude. The horizontal axis 1202represents time and is divided into two different time periods, ‘1’ and‘2’. Each time period corresponds to a different state for each set ofDBS electrodes 411 c-d. The two different time period allow the NBM andthe NAcc to receive DBS therapies or DBS pulses intermittently.

For example, during the time period ‘1’, the IPG 450 may configure orset the DBS electrodes 411 a-b through the switching circuitry 457 tothe anode state. Thereby the DBS electrodes 411 a-b emit DBS pulseamplitudes 1218 stimulating the NBM 1104. It should be noted that duringthe time period ‘1’, the DBS electrodes 411 c-d may be configured by theIPG 450 in an open or inactive state such that the DBS electrodes 411c-d are not emitting energy (e.g., the DBS pulse). During the timeperiod ‘2’, the IPG 450 may configure or set the DBS electrodes 411 a-bthrough the switching circuitry 457 to the open or inactive state.Thereby, the NDM 1104 is no longer stimulated by the DBS electrodes 411a-b. Conversely, the IPG 450 may configure or set the DBS electrodes 411c-d through the switching circuitry 475 to the anode state. Thereby, theDBS electrodes 411 c-d emit the DBS pulse amplitudes 1220 stimulatingthe NAcc 1102. It should be noted that even though the DBS pulses 1210,1212, 1214, and 1216 are illustrated as monophasic pulses other pulseconfigurations are possible within the time periods ‘1’ and ‘2’, such asbiphasic pulses. Optionally, additional time period may be used based onalternative stimulation programs used in different embodiments.

Optionally, as shown in FIG. 13, a DBS lead 1310 may be positioned suchthat DBS electrodes 1305 a-c may be divided into two sets or combinationof DBS electrodes 1305 a-b and 1305 b-c with a common DBS electrode 1305b. Each set of DBS electrodes 1305 a-b and 1305 b-c have energytrajectories 1312 and 1302, respectively, that may stimulate twodifferent DBS targets, such as NDM 1304 and NAcc 1306.

Optionally, the IPG 450 may be programmed or configured by theprogrammer unit 136 to deliver DBS pulses or stimulate DBS targetsthrough the DBS electrodes 411 a-d to manage or slow down a progressionof AD.

Optionally, the IPG 450 may be programmed or configured by theprogrammer unit 136 to deliver DBS pulses or stimulate DBS targetsthrough the DBS electrodes 411 a-d in a current regulated and/or chargebalance manner.

Optionally, the performing of DBS therapy may include maintainingparameters associated with the DBS pulse constant for an extended waitperiod of time while testing for a present of acute or sub-acute sideeffect (e.g., dysfunctional illumination, hearing issues, or the like),following the wait period of time adjusting the parameters.

For example, the DBS lead 410 is implanted within the implantationcoordinates and coupled to the IPG 450. Once implanted, the user mayperform a testing sequence emitted from the DBS electrodes 411 a-d asDBS pulses. The testing sequence may be initiated by the user using theuser interface 130, which communicates to the programmer unit 136. TheIPG 450 may receive the testing sequence instructions from theprogrammer unit 136 with predetermined DBS pulses that are emitted fromthe DBS electrodes 411 a-d. During the testing sequence, the user ordoctor may test the eye sight of the patient to determine if the patientis experiencing dysfunctional illumination or see flashes while the DBSpulses are emitted from the DBS electrodes 411 a-d. Dysfunctionalillumination may occur when the DBS lead 410 is implanted incorrectlywith respect to the NBM and will need to be moved.

Optionally, the performing of DBS therapy may include performing aglobal measure of cognitive function that include tests for at least oneof declarative memory, orientation, praxis, receptive language orexpressive language. For example, post implantation of the DBS lead 410the doctor may perform a series of examinations of the patient toconsciously recall facts, knowledge and/or past experiences of thepatient to test the declarative memory of the patient. Based on theexamination results, the doctor may alter or modify the DBS pulses(e.g., frequency, amplitude, state sequences) through the user interface130 by reprogramming the IPG 450 through the programmer unit 136.

The modules 106 and 118, the programmer unit 136, the IPG 450, andcontrol unit 116 may include any processor-based or microprocessor-basedsystem including systems using microcontrollers, reduced instruction setcomputers (RISC), application specific integrated circuits (ASICs),field-programmable gate arrays (FPGAs), logic circuits, and any othercircuit or processor capable of executing the functions describedherein. Additionally, or alternatively, the modules 106 and 118, theprogrammer unit 136, the IPG 450, and control unit 116 may representcircuit modules that may be implemented as hardware with associatedinstructions (for example, software stored on a tangible andnon-transitory computer readable storage medium, such as a computer harddrive, ROM, RAM, or the like) that perform the operations describedherein. The above examples are exemplary only, and are thus not intendedto limit in any way the definition and/or meaning of the term“controller.” The modules 106 and 118, the programmer unit 136, the IPG450, and control unit 116 may execute a set of instructions that arestored in one or more storage elements, in order to process data. Thestorage elements may also store data or other information as desired orneeded. The storage element may be in the form of an information sourceor a physical memory element within the modules 106 and 118, theprogrammer unit 136, the IPG 450, and control unit 116. The set ofinstructions may include various commands that instruct the modules 106and 118, the programmer unit 136, the IPG 450, and control unit 116 toperform specific operations such as the methods and processes of thevarious embodiments of the subject matter described herein. The set ofinstructions may be in the form of a software program. The software maybe in various forms such as system software or application software.Further, the software may be in the form of a collection of separateprograms or modules, a program module within a larger program or aportion of a program module. The software also may include modularprogramming in the form of object-oriented programming. The processingof input data by the processing machine may be in response to usercommands, or in response to results of previous processing, or inresponse to a request made by another processing machine.

As used herein, the terms “software” and “firmware” are interchangeable,and include any computer program stored in memory for execution by acomputer, including RAM memory, ROM memory, EPROM memory, EEPROM memory,and non-volatile RAM (NVRAM) memory. The above memory types areexemplary only, and are thus not limiting as to the types of memoryusable for storage of a computer program.

It is to be understood that the subject matter described herein is notlimited in its application to the details of construction and thearrangement of components set forth in the description herein orillustrated in the drawings hereof. The subject matter described hereinis capable of other embodiments and of being practiced or of beingcarried out in various ways. Also, it is to be understood that thephraseology and terminology used herein is for the purpose ofdescription and should not be regarded as limiting. The use of“including,” “comprising,” or “having” and variations thereof herein ismeant to encompass the items listed thereafter and equivalents thereofas well as additional items.

It is to be understood that the above description is intended to beillustrative, and not restrictive. For example, the above-describedembodiments (and/or aspects thereof) may be used in combination witheach other. In addition, many modifications may be made to adapt aparticular situation or material to the teachings of the inventionwithout departing from its scope. While the dimensions, types ofmaterials and coatings described herein are intended to define theparameters of the invention, they are by no means limiting and areexemplary embodiments. Many other embodiments will be apparent to thoseof skill in the art upon reviewing the above description. The scope ofthe invention should, therefore, be determined with reference to theappended claims, along with the full scope of equivalents to which suchclaims are entitled. In the appended claims, the terms “including” and“in which” are used as the plain-English equivalents of the respectiveterms “comprising” and “wherein.” Moreover, in the following claims, theterms “first,” “second,” and “third,” etc. are used merely as labels,and are not intended to impose numerical requirements on their objects.Further, the limitations of the following claims are not written inmeans-plus-function format and are not intended to be interpreted basedon 35 U.S.C. § 112(f), unless and until such claim limitations expresslyuse the phrase “means for” followed by a statement of function void offurther structure.

What is claimed is:
 1. A method for performing deep brain stimulation(DBS) therapy, the method comprising: pre-operatively acquiring at leastone pre-operative image of a brain of a patient with at least oneimaging sub-system; determining a location of a Nucleus Basalis ofMeynert (NBM) for therapy in the at least one pre-operative image;intra-operatively acquiring at least one intra-operative image of thebrain after obtaining an access opening through a skull of the patientand after positioning a fiducial on or within the brain through theaccess opening; performing surgical planning based on the at least onepre-operative image and the at least one intra-operative image;advancing a first lead having a first plurality of deep brainstimulation (DBS) electrodes to a first target position proximate to orwithin a first NBM area; advancing a second lead having a secondplurality of DBS electrodes to a second target position proximate to orwithin a second NBM area; coupling the first and second leads to animplantable pulse generator (IPG) configured to deliver DBS pulsesthrough the respective pluralities of DBS electrodes to the first andsecond NBM areas, the IPG to deliver DBS pulses for treating symptomsassociated with Alzheimer's Disease (AD); and delivering an NBM therapyutilizing a first subset of the first plurality of DBS electrodes tostimulate the first NBM area and delivering a Nucleus Accumbens (NAcc)therapy utilizing a second subset of the first plurality of DBSelectrodes to stimulate an NAcc area proximate to the first NBM area,the first and second subsets of the first plurality of DBS electrodeshaving at least one different electrode.
 2. The method of claim 1,wherein the first NBM area and the NAcc area are each stimulated byrespective DBS pulses having different amplitudes.
 3. The method ofclaim 2, wherein the surgical planning and advancing operations areperformed responsive to identifying a registered position of thefiducial on one or more of the at least one pre-operative image and theat least one intra-operative image.
 4. The method of claim 3, whereinthe first and second target positions are proximate to the first andsecond NBM areas respectively such that a surface of the first pluralityof DBS electrodes is within 5.0 mm of the first NBM area and a surfaceof the second plurality of DBS electrodes is within 5.0 mm of the secondNBM area.
 5. The method of claim 1, wherein the NBM therapy and the NAcctherapy are delivered intermittently.
 6. The method of claim 5, furthercomprising delivering the NBM therapy to the first NBM area when thefirst subset of the first plurality of DBS electrodes are configured tobe in a STIM ON state while the second subset of the first plurality ofthe DBS electrodes are in a STIM OFF state.
 7. The method of claim 5,further comprising delivering the NAcc therapy to the NAcc area when thefirst subset of the first plurality of DBS electrodes are configured tobe in a STIM OFF state while the second subset of the first plurality ofthe DBS electrodes are in a STIM ON state.
 8. The method of claim 1,further comprising performing a global measure of cognitive functionthat includes testing the patient for at least one of declarativememory, orientation, praxis, receptive language or expressive language.9. The method of claim 1, wherein the surgical planning and advancingoperations include the step of advancing the first lead to the firsttarget position such that the first plurality of DBS electrodes areoperative to be stimulated by DBS pulses having a particular amplitudefor generating an energy trajectory propagating from the first pluralityof DBS electrodes that covers the first NBM area and the NAcc areaproximate thereto.
 10. A system for performing deep brain stimulation(DBS) therapy, the system comprising: a surgical planning (SP) workstation having an input configured to receive at least one pre-operativeimage of a brain of a patient with at least one imaging sub-system; theSP work station configured to permit a user to determine a location of aNucleus Basalis of Meynert (NBM) for therapy in the at least onepre-operative image; the SP work station having an input configured toreceive at least one intra-operative image of the brain after obtainingan access opening through a skull of the patient and after positioning afiducial on or within the brain through the access opening; the SP workstation configured to perform surgical planning based on the at leastone pre-operative image and the at least one intra-operative image; afirst lead having a first plurality of deep brain stimulation (DBS)electrodes, the first lead configured to be advanced to a first targetposition proximate to or within a first NBM area; a second lead having asecond plurality of DBS electrodes, the second lead configured to beadvanced to a second target position proximate to or within a second NBMarea; an implantable pulse generator (IPG) coupled to the first andsecond leads, the IPG configured to deliver DBS pulses through therespective pluralities of DBS electrodes to the first and second NBMareas, the IPG configured to deliver DBS pulses for treating symptomsassociated with Alzheimer's Disease (AD); and the IPG further configuredto deliver an NBM therapy utilizing a first subset of the firstplurality of DBS electrodes to stimulate the first NBM area and todeliver a Nucleus Accumbens (NAcc) therapy utilizing a second subset ofthe first plurality of DBS electrodes to stimulate an NAcc areaproximate to the first NBM area, the first and second subsets of thefirst plurality of DBS electrodes having at least one differentelectrode.
 11. The system of claim 10, wherein the IPG is furtherconfigured to stimulate the first NBM area and the NAcc area byrespective DBS pulses having different amplitudes.
 12. The system ofclaim 10, wherein the SP work station is configured to perform thesurgical planning and advancing operations responsive to identifying aregistered position of the fiducial on one or more of the at least onepre-operative image and the at least one intra-operative image.
 13. Thesystem of claim 10, wherein the IPG is configured to deliver the NBMtherapy and the NAcc therapy intermittently.
 14. The system of claim 13,wherein the IPG is configured to deliver the NBM therapy to the firstNBM area when the first subset of the first plurality of DBS electrodesare configured by the IPG to be in a STIM ON state while the secondsubset of the first plurality of the DBS electrodes are in a STIM OFFstate.
 15. The system of claim 13, wherein the IPG is configured todeliver the NAcc therapy to the NAcc area when the first subset of thefirst plurality of DBS electrodes are configured by the IPG to be in aSTIM OFF state while the second subset of the first plurality of the DBSelectrodes are in a STIM ON state.
 16. The system of claim 10, whereinthe IPG includes pulse generating circuitry configured to deliver DBSpulses having a particular amplitude for generating an energy trajectorypropagating from the first plurality of DBS electrodes that covers atleast a portion of both the first NBM area and the NAcc area proximatethereto.